The present invention involves microfluidic network structures, methods for fabricating microfluidic network structures, and methods for using such structures.
The need for complexity in microfluidic systems is increasing rapidly as sophisticated functionsxe2x80x94chemical reactions and analyses, bioassays, high-throughput screens, and sensorsxe2x80x94are being integrated into single microfluidic devices. Complex systems of channels require more complex connectivity than can be generated in conventional two-dimensional microfluidic systems having a single level of channels, since such typical single-level designs do not allow two channels to cross without fluidically connecting. Most methods for fabricating microfluidic channels are based on photolithographic procedures, and yield such two-dimensional systems. There are a number of more specialized procedures, such as stereolithography (see for example, K. Ikuta, K. Hirowatari, T. Ogata, Proc. IEEE MEMS""94, Oiso, Japan, Jan. 25-28, 1994, pp. 1-6), laser-chemical three-dimensional writing (see for example, T. M. Bloomstein, D. J. Ehrlich, J Vac. Sci. Technol. B, Vol. 10, pp. 2671-2674, 1992), and modular assembly (see for example, C. Gonzalez, R. L. Smith, D. G. Howitt, S. D. Collins, Sens. Actuators A, Vol. 66, pp. 315-332, 1998), that yield three-dimensional structures, but these methods are typically time consuming, difficult to perform, and expensive, and are thus not well suited for either prototyping or manufacturing, and are also not capable of making certain types of structures. Better methods for generating complex three-dimensional microfluidic systems are needed to accelerate the development of microfluidic technology. The present invention, in some embodiments, provides such improved methods for generating complex three-dimensional microfluidic systems.
It is known to use a stamp or mold to transfer patterns to a surface of a substrate, (see for example, R. S. Kane, S. Takayama, E. Ostuni, D. E. Ingber, G. M. Whitesides, Biomaterials, Vol. 20, pp. 2363-2376, 1999; and Y. Xia, G. M. Whitesides, Angew. Chem. Int. Ed. Engl., Vol. 37, pp. 551-575, 1998; U.S. Pat. No. 5,512,131; International Pat. Publication No. WO 97/33737, published Sep. 18, 1997). Most conventional soft lithographic techniques, for example, microcontact printing (xcexcCP) (see for example, C. S. Chen, M. Mrksich, S. Huang, G. M. Whitesides, D. E. Ingber, Science, Vol. 276, pp. 1425-1428, 1997; A. Bernard, E. Delamarche, H. Schmid, B. Michel, H. R. Bosshard, H. Biebuyck, Langmuir, Vol. 14, pp. 2225-2229, 1998) and micromolding in capillaries (MIMIC) (see for example, N. L. Jeon, I. S. Choi, B. Xu, G. M. Whitesides, Adv. Mat., Vol. 11, pp. 946-949, 1999; E. Delamarche, A. Bernard, H. Schmid, B Michel, H. Biebuyck, Science, Vol. 276, pp. 779-781, 1997; E. Delamarche, A. Bernard, H. Schmid, A. Bietsch, B. Michel, h. Biebuyck, J. Am. Chem. Soc., Vol. 120, pp. 500-508, 1998; A. Folch, A. Ayon, O. Hurtado, M. A. Schmidt, M. Toner, J. Biomech. Eng., Vol. 121, pp. 28-34, 1999; A. Folch, M. Toner, Biotech. Prog., Vol. 14, pp. 388-392, 1998), have been limited to procedures that pattern one substance at a time, or to relatively simple, continuous patterns. These constraints are both topological and practical. The surface of a stamp in xcexcCP, or of a channel system in MIMIC, is effectively a two-dimensional structure. In xcexcCP, this two-dimensionality of the stamp limits the types of patterns that can be transferred to those comprising a single xe2x80x9ccolorxe2x80x9d of ink in the absence of a way of selectively xe2x80x9cinkingxe2x80x9d different regions of the stamp with different materials. Patterning of multiple xe2x80x9cinksxe2x80x9d using conventional methods requires multiple steps of registration and stamping. In MIMIC, the two-dimensional channel system limits patterning to relatively simple, continuous structures or requires multiple patterning steps.
There remains a general need in the art for improved methods for forming patterns on surfaces with soft lithographic techniques, and for providing techniques able to pattern onto a surface arbitrary two-dimensional patterns and able to form complex patterns comprised of multiple regions, where different regions of the pattern can comprise different materials, on a surface without the need for multiple steps of registration or stamping and without the need to selectively xe2x80x9cinkxe2x80x9d different regions of the stamp with different materials. The present invention, in some embodiments, provides such improved methods for forming patterns on surfaces with soft lithographic techniques.
The present invention involves, in certain embodiments, improved microfluidic systems and procedures for fabricating improved microfluidic systems, which contain one or more levels of microfluidic channels. The inventive methods can provide a convenient route to topologically complex and improved microfluidic systems. The present invention also, in some embodiments, involves microfluidic systems and methods for fabricating complex patterns of materials, such as biological materials and cells, on surfaces. In such embodiments, the invention involves microfluidic surface patterning systems and methods for fabricating complex, discontinuous patterns on surfaces that can incorporate or deposit multiple materials onto a surface. The present invention, in some embodiments, can provide improved stamps for microcontact surface patterning able to pattern onto a surface arbitrary two-dimensional patterns and able to pattern multiple substances onto a surface without the need for multiple steps of registration or stamping during patterning and without the need to selectively xe2x80x9cinkxe2x80x9d different regions of the stamp with different materials.
According to one embodiment of the invention, a microfluidic network is disclosed. The microfluidic network comprises a polymeric structure including therein at least a first and a second non-fluidically interconnected fluid flow paths. At least the first flow path comprises a series of interconnected channels within the polymeric structure. The series of interconnected channels includes at least one first channel disposed within a first level of the structure, at least one second channel disposed within a second level of the structure, and at least one connecting channel fluidically interconnecting the first channel and the second channel. At least one channel within the structure has a cross-sectional dimension not exceeding about 500 xcexcm. The structure includes at least one channel disposed within the first level of the structure that is non-parallel to at least one channel disposed within the second level of the structure.
In another embodiment of the invention, a microfluidic network is disclosed. The microfluidic network comprises an elastomeric structure including therein at least one fluid flow path. The flow path comprises a series of interconnected channels within the structure. The series of interconnected channels includes at least one first channel disposed within a first level of the structure, at least one second channel disposed within a second level of the structure, and at least one connecting channel fluidically interconnecting the first channel and the second channel. At least one channel within the structure has a cross-sectional dimension not exceeding about 500 xcexcm, and the structure includes at least one channel disposed within the first level of the structure that is non-parallel to at least one channel disposed within the second level of the structure.
In yet another embodiment, a polymeric membrane is disclosed. The polymeric membrane comprises a first surface including at least one channel disposed therein, a second surface including at least one channel disposed therein, and a polymeric region intermediate the first surface and the second surface. The intermediate region includes at least one connecting channel therethrough fluidically interconnecting the channel disposed in the first surface and the channel disposed in the second surface of the membrane. At least one channel has a cross-sectional dimension not exceeding about 500 xcexcm.
In another embodiment of the invention, a method for forming a microfluidic network structure is disclosed. The method comprises providing at least one mold substrate, forming at least one topological feature on a surface of the mold substrate to form a first mold master, contacting the surface with a first hardenable liquid, hardening the liquid thereby creating a first molded replica of the surface, removing the first molded replica from the first mold master, and assembling the first molded replica into a structure comprising a microfluidic network. The assembled microfluidic network structure has at least one fluid flow path comprising a series of interconnected channels within the structure. The series of interconnected channels includes at least one first channel disposed within a first level of the structure, at least one second channel disposed within a second level of the structure, and at least one connecting channel fluidically interconnecting the first channel and the second channel. At least one of the channels within the structure has a cross-sectional dimension not exceeding about 500 xcexcm. The structure includes at least one channel disposed within the first level of the structure that is non-parallel to at least one channel disposed within the second level of the structure.
In yet another embodiment, a method for forming a molded structure is disclosed. The method comprises providing at least one mold substrate and forming at least one two-level topological feature having at least one lateral dimension not exceeding 500 xcexcm on a surface of the substrate to form a mold master. The two-level topological feature is characterized by a first portion having a first depth or height with respect to a region of the surface adjacent to the feature, and a second portion integrally connected with the first portion having a second depth or height with respect to the region of the surface adjacent to the feature that is greater than the first depth or height. The method further comprises contacting the surface with a hardenable liquid, hardening the liquid thereby creating a molded replica of the surface, and removing the molded replica from the mold master.
In another embodiment of the invention, a method for forming topological features on a surface of a material is disclosed. The method comprises exposing portions of a surface of a first layer of photoresist to radiation in a first pattern, coating the surface of the first layer of photoresist with a second layer of photoresist, exposing portions of a surface of the second layer of photoresist to radiation in a second pattern different from the first pattern, and developing the first and second photoresist layers with a developing agent. The developing step yields a positive relief pattern in photoresist that includes at least one two-level topological feature having at least one cross-sectional dimension not exceeding 500 xcexcm. The two-level topological feature is characterized by a first portion having a first height with respect to the surface of the material and a second portion, integrally connected to the first portion, having a second height with respect to the surface of the material.
In yet another embodiment, a method for forming a molded structure is disclosed. The method involves providing a first mold master having a surface formed of an elastomeric material and including at least one topological feature with at least one cross-sectional dimension not exceeding about 500 xcexcm thereon. The method further comprises providing a second mold master having a surface including at least one topological feature with at least one cross-sectional dimension not exceeding about 500 xcexcm thereon. The method further comprises placing a hardenable liquid in contact with the surface of at least one of the first and second mold master, bringing the surface of the first mold master into at least partial contact with the surface of the second mold master, hardening the liquid thereby creating a molded replica of the surface of the first mold master and the surface of the second mold master, and removing the molded replica from at least one of the mold masters.
In another embodiment of the invention, a method for forming a molded structure is disclosed. The method involves providing a first mold master having a surface including at least a first topological feature with at least one cross-sectional dimension not exceeding about 500 xcexcm thereon and at least a second topological feature comprising a first alignment element. The method further comprises providing a second mold master having a surface including at least a first topological feature with at least one cross-sectional dimension not exceeding about 500 xcexcm thereon and at least a second topological feature comprising a second alignment element having a shape that is mateable to the shape of the first alignment element. The method further comprises placing a hardenable liquid in contact with the surface of at least one of the first and second mold master, bringing the surface of the first mold master into at least partial contact with the surface of the second mold master, aligning the first topological features of the first and second mold masters with respect to each other by adjusting a position of the first mold master with respect to a position of the second mold master until the first alignment element matingly engages and interdigitates with the second alignment element, hardening the liquid thereby creating a molded replica of the surface of the first mold master and the surface of the second mold master, and removing the molded replica from at least one of the mold masters.
In yet another embodiment of the invention, a method for aligning and sealing together surfaces is disclosed. The method comprises disposing two surfaces, at least one of which is oxidized, adjacent to each other such that they are separated from each other by a continuous layer of a liquid that is essentially non-reactive with the surfaces, aligning the surfaces with respect to each other, and removing the liquid from between the surfaces, thereby sealing the surfaces together via a chemical reaction between the surfaces.
In another embodiment of the invention, a method for molding an article is disclosed. The method comprises providing a first mold master having a surface with a first set of surface properties and providing a second mold master having a surface with a second set of surface properties. At least one of the first and second mold masters has a surface including at least one topological feature with at least one cross-sectional dimension not exceeding about 500 xcexcm thereon. The method further comprises placing a hardenable liquid in contact with the surface of at least one of the first and second mold masters, bringing the surface of the first mold master into at least partial contact with the surface of the second mold master, hardening the liquid thereby creating a molded replica of the surface of the first mold master and the surface of the second mold master, separating the mold masters from each other, and removing the molded replica from the surface of the first mold master while leaving the molded replica in contact with and supported by the surface of the second mold master.
In yet another embodiment, a microfluidic network is disclosed. The microfluidic network comprises a polymeric structure including therein at least a first and a second non-fluidically interconnected fluid flow paths. The first flow path comprises at least two non-colinear interconnected channels disposed within a first plane, and the second flow path comprises at least one channel disposed within a second plane that is non-parallel with the first plane. At least one channel within the structure has a cross-sectional dimension not exceeding about 500 xcexcm.
In another embodiment of the invention, a microfluidic network is disclosed. The microfluidic network comprises a polymeric structure including therein at least one fluid flow path. The fluid flow path is formed of at least one channel and has a longitudinal axis defined by the direction of bulk fluid flow within the flow path. The longitudinal axis of the flow path is not disposed within any single plane.
In another embodiment of the invention, a method of patterning a material surface is disclosed. The method comprises providing a stamp having a structure including at least one flow path comprising a series of interconnected channels within the structure. The series of interconnected channels includes at least one first channel disposed within an interior region of the structure, at least one second channel disposed within a stamping surface of the structure defining a first pattern therein, and at least one connecting channel fluidically interconnecting the first channel and the second channel. The method further comprises contacting the stamping surface with a portion of the material surface, and, while maintaining the stamping surface in contact with the portion of the material surface, at least partially filling the flow path with a fluid so that at least a portion of the fluid contacts the material surface.
In yet another embodiment, a method of patterning a material surface is disclosed. The method comprises providing a stamp having a structure including at least two non-fluidically interconnected flow paths therein including a first fluid flow path defining a first pattern of channels disposed within a stamping surface of the structure and a second fluid flow path defining a second pattern of channels disposed within the stamping surface of the structure. Each of the first and second patterns of channels is non-continuous, and the channels defining the first pattern are non-intersecting with the channels defining the second pattern. The method further comprises contacting the stamping surface with a portion of the material surface, while maintaining the stamping surface in contact with the portion of the material surface, at least partially filling the first flow path with a first fluid so that at least a portion of the first fluid contacts the material surface and at least partially filling the second flow path with a second fluid so that at least a portion of the second fluid contacts the material surface, and removing the stamping surface to provide a pattern on the material surface according to the first pattern, which is formed by contact of the material surface with the first fluid, and according to the second pattern, which is formed by contact of the material surface with the second fluid.
In another embodiment, a method of patterning a material surface is disclosed. the method involves providing a stamp having a structure including at least one non-linear fluid flow path therein in fluid communication with a stamping surface of the structure. The method further involves contacting the stamping surface with a portion of the material surface and, while maintaining the stamping surface in contact with the portion of the material surface, at least partially filling the flow path with a fluid so that at least a portion of the fluid contacts the material surface.
Other advantages, novel features, and objects of the invention will become apparent from the following detailed description of the invention when considered in conjunction with the accompanying drawings, which are schematic and which are not intended to be drawn to scale. In the figures, each identical or nearly identical component that is illustrated in various figures is represented by a single numeral. For purposes of clarity, not every component is labeled in every figure, nor is every component of each embodiment of the invention shown where illustration is not necessary to allow those of ordinary skill in the art to understand the invention.